Measurement of the K + - pi + pi - e + - (-) v e form factors and of the pi pi scattering length a 0 0

The quark condensate is a fundamental free parameter of Chiral Perturbation Theory ($chi PT$), since it determines the relative size of the mass and momentum terms in the power expansion. In order to confirm or contradict the assumption of a large quark condensate, on which $chi PT$ is based, experimental tests are needed. In particular, the $S$-wave $pipi$ scattering lengths $a_0^0$ and $a_0^2$ can be predicted precisely within $chi PT$ as a function of this parameter and can be measured very cleanly in the decay $K^{pm} to pi^{+} pi^{-} e^{pm} stackrel{mbox{tiny(---)}}{nu_e}$ ($K_{e4}$). About one third of the data collected in 2003 and 2004 by the NA48/2 experiment were analysed and 342,859 $K_{e4}$ candidates were selected. The background contamination in the sample could be reduced down to 0.3% and it could be estimated directly from the data, by selecting events with the same signature as $K_{e4}$, but requiring for the electron the opposite charge with respect to the kaon, the so-called ``wrong sign'' events. This is a clean background sample, since the kaon decay with $Delta S=-Delta Q$, that would be the only source of signal, can only take place through two weak decays and is therefore strongly suppressed. The Cabibbo-Maksymowicz variables, used to describe the kinematics of the decay, were computed under the assumption of a fixed kaon momentum of 60 GeV/$c$ along the $z$ axis, so that the neutrino momentum could be obtained without ambiguity. The measurement of the form factors and of the $pipi$ scattering length $a_0^0$ was performed in a single step by comparing the five-dimensional distributions of data and MC in the kinematic variables. The MC distributions were corrected in order to properly take into account the trigger and selection efficiencies of the data and the background contamination. The following parameter values were obtained from a binned maximum likelihood fit, where $a_0^2$ was expressed as a function of $a_0^0$ according to the prediction of chiral perturbation theory: f'_s/f_s = 0.133+- 0.013(stat)+- 0.026(syst) f''_s/f_s = -0.041+- 0.013(stat)+- 0.020(syst) f_e/f_s = 0.221+- 0.051(stat)+- 0.105(syst) f'_e/f_s = -0.459+- 0.170(stat)+- 0.316(syst) tilde{f_p}/f_s = -0.112+- 0.013(stat)+- 0.023(syst) g_p/f_s = 0.892+- 0.012(stat)+- 0.025(syst) g'_p/f_s = 0.114+- 0.015(stat)+- 0.022(syst) h_p/f_s = -0.380+- 0.028(stat)+- 0.050(syst) a_0^0 = 0.246+- 0.009(stat)+- 0.012(syst)}+- 0.002(theor), where the statistical uncertainty only includes the effect of the data statistics and the theoretical uncertainty is due to the width of the allowed band for $a_0^2$.

In vivo and in vitro investigation of the tissue-specific activity of the human CYP3A4 and CYP3A5 promoters

The human cytochrome P450 3A4 (CYP3A4), the predominant but variably expressed cytochrome P450 in adult liver and small intestine is involved in the metabolism of over 50% of currently used drugs. Its paralog CYP3A5 plays a crucial role in the disposition of several drugs with low therapeutic index, including tacrolimus. Limited information is available for the CYP3A5 transcriptional regulation and its induction by xenobiotics remains controversial. In the first part of this study, we analysed the CYP3A5 transcriptional regulation and its induction by xenobiotics in vivo using transgenic mice. To this end, two transgenic strains were established by pronuclear injection of a plasmid, expressing firefly luciferase driven by a 6.2 kb of the human CYP3A5 promoter. A detailed analysis of both strains shows a tissue distribution largely reflecting that of CYP3A5 transcripts in humans. Thus, the highest luciferase activity was detected in the small intestine, followed by oesophagus, testis, lung, adrenal gland, ovary, prostate and kidney. However, no activity was observed in the liver. CYP3A5-luc transgenic mice were similarly induced in both sexes with either PCN or TCPOBOP in small intestine in a dose-dependent manner. Thus, the 6.2 kb upstream promoter of CYP3A5 mediates the broad tissue activity in transgenic mice. CYP3A5 promoter is inducible in the small intestine in vivo, which may contribute to the variable expression of CYP3A in this organ. rnThe hepato-intestinal level of the detoxifying oxidases CYP3A4 and CYP3A5 is adjusted to the xenobiotic exposure mainly via the xenosensor and transcriptional factor PXR. CYP3A5 is additionally expressed in several other organs lacking PXR, including kidney. In the second part of this study, we investigated the mechanism of the differential expression of CYP3A5 and CYP3A4 and its evolutionary origin using renal and intestinal cells, and comparative genomics. For this examination, we established a two-cell line models reflecting the expression relationships of CYP3A4 and CYP3A5 in the kidney and small intestine in vivo. Our data demonstrate that the CYP3A5 expression in renal cells was enabled by the loss of a suppressing Yin Yang 1 (YY1)-binding site from the CYP3A5 promoter. This allowed for a renal CYP3A5 expression in a PXR-independent manner. The YY1 element is retained in the CYP3A4 gene, leading to its suppression, perhaps via interference with the NF1 activity in renal cells. In intestinal cells, the inhibition of CYP3A4 expression by YY1 is abrogated by a combined activating effect of PXR and NF1 acting on their respective response elements located adjacent to the YY1-binding site on CYP3A4 proximal promoter. CYP3A4 expression is further facilitated by a point mutation attenuating the suppressing effect of YY1 binding site. The differential expression of CYP3A4 and CYP3A5 in these organs results from the loss of the YY1 binding element from the CYP3A5 promoter, acting in concert with the differential organ expression of PXR, and with the higher accumulation of PXR response elements in CYP3A4. rn

Parity violating asymmetry in the electron deuteron quasielastic scattering, strange vector and axial vector form factors and beam normal spin asymmetries

In dieser Arbeit wurde die paritätsverletzende Asymmetrie in derrnquasielastischen Elektron-Deuteron-Streuung bei Q^2=0.23 (GeV/c)^2 mitrneinem longitudinal polarisierten Elektronstrahl bei einer Energie von 315rnMeV bestimmt. Die Messung erfolgte unter Rückwärtswinkeln. Der Detektor überdeckte einen polaren Streuwinkelbereichrnzwischen 140 und 150 deg. Das Target bestand aus flüssigemrnDeuterium in einer Targetzelle mit einer Länge von 23.4 cm. Dierngemessene paritätsverletzende Asymmetrie beträgt A_{PV}^d = (-20.11 pm 0.87_{stat} pm 1.03_{syst}), wobei der erste Fehler den statistischenrnFehlereitrag und der zweite den systematischen Fehlerbeitrag beschreibt. Ausrnder Kombination dieser Messung mit Messungen der paritätsverletzendenrnAsymmetrie in der elastischen Elektron-Proton-Streuung bei gleichem Q^2rnsowohl bei Vorwärts- als auch bei Rückwärtsmessungen können diernVektor-Strange-Formfaktoren sowie der effektive isovektorielle und isoskalarernVektorstrom des Protons, der die elektroschwachen radiativen Anapolkorrekturenrnenthält, bestimmt werden. Diese Arbeit umfasst ausserdem die Bestimmungrnder Asymmetrien bei einem transversal polarisierten Elektronstrahl sowohl beirneinem Proton- als auch einem Deuterontarget unter Rückwärtswinkeln beirnImpulsüberträgen von Q^2=0.10 (GeV/c)^2, Q^2=0.23 (GeV/c)^2rnund Q^2=0.35 (GeV/c)^2. Die im Experiment beobachteten Asymmetrien werdenrnmit theoretischen Berechnungen verglichen, welche den Imaginärteil der Zweiphoton-Austauschamplitude beinhalten.